Vasopeptidase Inhibition Has Potent Effects on Blood Pressure and Resistance Arteries in Stroke-Prone Spontaneously Hypertensive Rats

摘要: Abstract —The antihypertensive agent omapatrilat represents a novel approach to therapy, namely vasopeptidase inhibition. Omapatrilat (BMS-186716) concomitantly inhibits neutral endopeptidase and angiotensin-converting enzyme, leading protection from degradation of natriuretic other hypotensive peptides in addition interruption the renin-angiotensin system. Although potency on reduction blood pressure has been reported, its effects resistance artery structure function were unknown. We tested stroke-prone spontaneously hypertensive rats (SHRSP), malignant model hypertension, with hypothesis that it would improve endothelial mesenteric arteries. Ten-week-old SHRSP treated orally for 10 weeks (40 mg/kg per day). Mesenteric arteries (lumen <300 μm) studied pressurized myograph. After weeks, untreated had systolic 230±2 mm Hg was significantly reduced ( P <0.05) by (145±3 Hg). treatment improved endothelium-dependent relaxation as elicited acetylcholine (10−5 mol/L) but no significant effect endothelium-independent produced nitric oxide donor (sodium nitroprusside). This suggested there existed dysfunction corrected inhibition, probably part caused potent pressure–lowering omapatrilat. Media width media/lumen ratio decreased omapatrilat, trend =0.07) increase lumen diameter observed. Vascular stiffness (slope elastic modulus versus stress curve) unaltered In conclusion, acting agent, may SHRSP, severe form genetic hypertension.